How Can Men Destined for Biochemical Failure After Androgen Deprivation and Radiotherapy Be Identified Earlier?

Abstract

Purpose-The significance of prostate-specific antigen (PSA) increases during the recovery of androgen after androgen deprivation therapy (ADT) and radiotherapy for prostate cancer is not well understood. This study sought to determine whether the initial PSA increase from undetectable after completion of all treatment predicts for eventual biochemical failure (BF). Methods and Materials-Between July 1992 and March 2004, 163 men with a Gleason score of 8-10 or initial PSA level >20 ng/mL, or Stage T3 prostate cancer were treated with radiotherapy (median dose, 76 Gy) and ADT and achieved an undetectable PSA level. The first detectable PSA level after the cessation of ADT was defined as the PSA sentinel rise (SR). A PSA-SR of >0.25, >0.5, >0.75, and >1.0 ng/mL was studied as predictors of BF (nadir plus 2 ng/mL). Cox proportional hazards models were used for univariate and multivariate analyses for BF adjusting for pretreatment differences in Gleason score, stage, PSA level (continuous), dose (continuous), and ADT duration (<12 vs. ≥12 months).Results-Of the 163 men, 41 had BF after therapy. The median time to BF was 25 months (range, 4-96). The 5-year BF rate stratified by a PSA-SR of ≤0.25 vs. >0.25 ng/mL was 28% vs. 43% (p = 0.02), ≤0.5 vs. >0.5 ng/mL was 30% vs. 56% (p = 0.0003), ≤0.75 vs. >0.75 ng/mL was 29% vs. 66% (p < 0.0001), and ≤1.0 vs. >1.0 ng/mL was 29% vs. 75% (p < 0.0001). All four PSA-SRs were independently predictive of BF on multivariate analysis. Conclusion-The PSA-SR predicts for BF. A PSA-SR of >0.5 ng/mL can be used for early identification of men at greater risk of BF.

Impact of biochemical failure classification on clinical outcome: A secondary analysis ofRadiationTherapyOncologyGroup 9202 and 9413

“…Because the definition of 3 consecutive rises is known to be more susceptible to PSA bounces or benign rises in PSA after the cessation of ADT, that is one factor that might underlie the more favorable outcomes for those whose failure was determined by 3 consecutive rises. 16 Nevertheless, if patients were diagnosed with BF on the basis of 3 consecutive rises in the setting of false-positive BF, it also seems likely that patients would also have high false-positive rates if they had rising PSA levels but had not reached 3 consecutive rises and were started on ADT as part of the A2 group, and indeed this group (pattern 2; Table 2) appeared to have very favorable clinical outcomes, with a 90.3% 5-year survival rate and only a 7.9% DM rate. Interestingly, for those with A1 BF who had a rising PSA level after a nadir, the absolute nadir achieved was not prognostic for outcomes, whereas the rate of the PSA rise after a nadir was prognostic.…”

An Update on the Changing Indications for Androgen Deprivation Therapy for Prostate Cancer

“…This approach includes the incorporation of known risk factors for recurrent aggressive disease to define which patients need more aggressive early therapy and which patients may be able to be spared the adverse events of androgen deprivation at the detection of biochemical recurrence. The elements of risk stratification may include pretreatment PSA, PSA velocity, Gleason score, volume of tumor or stage [ 55 – 57 ], PSA velocity or total value [ 38 , 58 ], PSA nadir and time to recurrence after therapy [ 59 , 60 ], and possibly the presence of circulating tumor cells [ 61 ], as all of these have been shown to be associated with increased risk of progression or death from prostate cancer.…”

Update on the management of prostate cancer with goserelin acetate: patient perspectives

“…This approach includes the incorporation of known risk factors for recurrent aggressive disease to define which patients need more aggressive, early therapy and which patients may be able to be spared the adverse events of androgen deprivation at the detection of biochemical recurrence. The elements of risk-stratification may include pretreatment PSA, PSA velocity, Gleason score, volume of tumor or stage, [36][37][38] PSA velocity or total value, 29,39 PSA nadir and time to recurrence after therapy 40,41 and possibly the presence of circulating tumor cells, 42 as all of these have been shown to be associated with increased risk of progression or death from prostate cancer. …”